Premium
A comparison of left and right atrial fibroblasts reveals different collagen production activity and stress‐induced mitogen‐activated protein kinase signalling in rats
Author(s) -
Chung C.C.,
Kao Y.H.,
Yao C.J.,
Lin Y.K.,
Chen Y.J.
Publication year - 2017
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12835
Subject(s) - mitogen activated protein kinase , protein kinase a , microbiology and biotechnology , kinase , signalling , medicine , chemistry , biology
Aim Atrial fibrosis plays a pivotal role in the pathophysiology of heart failure ( HF ). The left atrium ( LA ) experiences greater fibrosis than the right atrium ( RA ) during HF . It is not clear whether LA cardiac fibroblasts contain distinctive activities that predispose LA to fibrosis. Methods LA and RA fibrosis were evaluated in healthy and isoproterenol‐induced HF Sprague Dawley rats. Rat LA and RA primary isolated fibroblasts were subjected to proliferation assay, oxidative stress assay, cell migration analysis, collagen measurement, cytokine array and Western blot. Results Healthy rat LA and RA had a similar extent of collagen deposition. HF significantly increased fibrosis to a greater severity in LA than in RA . Compared to isolated RA fibroblasts, the in vitro experiments showed that isolated LA fibroblasts had higher oxidative stress and exhibited higher collagen, transforming growth factor‐ β 1, connective tissue growth factor production and less vascular endothelial growth factor ( VEGF ) production, but had similar migration, myofibroblast differentiation and proliferation activities. VEGF significantly increased the collagen production ability of LA fibroblasts, but not RA fibroblasts. LA fibroblasts had more phosphorylated ERK 1/2 and P38 expression. ERK inhibitor ( PD 98059, 50 μ mol L −1 ) significantly attenuated collagen production and increased VEGF production in RA fibroblasts but not in LA fibroblasts. P38 inhibitor ( SB 203580, 30 μ mol L −1 ) significantly attenuated collagen production in LA fibroblasts but not in RA fibroblasts. P38 inhibitor also significantly increased VEGF production in RA and LA fibroblasts. Conclusions Differences in profibrotic activity between LA and RA fibroblasts may be caused by different responses to mitogen‐activated protein kinase signalling.